This invention relates to novel dehydrogenation processes, and more specifically, it relates to the treatment of arylimidazolidones with noble metal catalysts to provide the corresponding arylimidazolinones.
There is a need for the synthesis of various imidazothiazoles since such materials have a number of uses. The synthesis of such materials can also involve the preparation of one or another specific enantiomer. Exemplary of such bicyclic materials is tetramisole, or 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thiazole.
The synthesis of L-(-)-tetramisole, also known as "levamisole", is of great commercial interest because of its great activity as an anthelminthic, as disclosed in U.S. Pat. No. 3,463,786. One newly discovered process for preparing levamisole is a catalytic asymmetric synthesis through reduction of prochiral intermediates. The asymmetric reduction is achieved through catalysis by homogeneous asymmetric rhodium complexes acting on prochiral 1,4-disubstituted-4-imidazolin-2-ones. The maximum enantioselectivity shown was a 33% enantiomeric excess attained with a catalyst system derived from (+)-DIOP and [Rh(COD)]Cl.sub.2 acting on 1-(2-methoxyethyl)-3-acetyl-4-phenyl-4-imidazolin-2-one. The reduced product is converted to levamisole with retention of chirality.
Reduction of various substituted prochiral olefins using homogeneous asymmetric complexes of rhodium (I) salts as catalysts is a field that has been extensively examined in recent years. A review of the state of this art by H. B. Kagan has recently appeared in Pure and Applied Chem., 43, 401 (1976). For specific prochiral substrates the degree of enantioselectivity achieved in reduction has been found to be strongly influenced by the choice of the asymmetric tertiary phosphine derivative employed as a ligand in the catalyst complex.
A very high enantioselectivity of 63% enantiomeric excess in a reduced product is attained by catalytic reduction of the aforesaid imidazolin-2-one using a complex derived from (RhCODI).sub.2 and (+)-trans-bis-(1,2-diphenylphosphinomethyl)cyclobutane. The same degree of enantioselectivity has also been attained using the complex derived from [Rh(COD)I].sub.2 and (-)trans bicyclo (2,2,1) bis-(2,3-diphenylphosphinomethyl)heptane.
Maximum enantioselectivity attained through these and related processes is a 63% enantiomeric excess. In other words, the product contains 63% of the S-isomer and 37% of the RS racemate. While these yields permit 63% of the reduced product to be converted to optically pure, physiologically active levamisole, the 37% of racemate would merely produce tetramisole upon reduction, and this would have to be resolved conventionally.